scholarly journals Case Report: Ipilimumab-Induced Panhypophysitis: An Infrequent Occurrence and Literature Review

2020 ◽  
Vol 10 ◽  
Author(s):  
Agnese Barnabei ◽  
Silvia Carpano ◽  
Alfonsina Chiefari ◽  
Marta Bianchini ◽  
Rosa Lauretta ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Laboratory Tests ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Cortisone Acetate ◽  
Posterior Pituitary ◽  
Case Presentation ◽  
Normal Ranges ◽  
Fourth Cycle ◽  
Anticancer Response

BackgroundImmune checkpoint inhibitors (ICIs), by unleashing the anticancer response of the immune system, can improve survival of patients affected by several malignancies, but may trigger a broad spectrum of adverse events, including autoimmune hypophysitis. ICI-related hypophysitis mainly manifests with anterior hypopituitarism, while the simultaneous involvement of both anterior and posterior pituitary (i.e., panhypophysitis) has rarely been described.Case PresentationIn June 2015, a 64-year-old man affected by liver metastases of a uveal melanoma was referred to us due to polyuria and polydipsia. Two months prior, he had started ipilimumab therapy (3 mg/kg iv every 21 days). The treatment was well-tolerated (only mild asthenia and diarrhea were reported). A few days before the fourth cycle, the patient complained of intense headaches, profound fatigue, nocturia, polyuria (up to 10 L urine/daily), and polydipsia. Laboratory tests were consistent with adrenal insufficiency, hypothyroidism, and transient central diabetes insipidus. The pituitary MRI showed an enlarged gland with microinfarcts, while the hypophyseal stalk was normal, and the neurohypophyseal ‘bright signal’ in T1 sequences was not detected. The treatment included dexamethasone (then cortisone acetate at replacement dose), desmopressin, and levothyroxine. Within the next five days, the symptoms resolved, and blood pressure, electrolytes, glucose, and urinalysis were stable within the normal ranges; desmopressin was discontinued while cortisone acetate and levothyroxine were maintained. The fourth ipilimumab dose was entirely administered in the absence of further side effects.ConclusionAs ICIs are increasingly used as anticancer agents, the damage to anterior and/or posterior pituitary can be progressively encountered by oncologists and endocrinologists in their clinical practice. Patients on ICIs and their caregivers should be informed about that risk and be empowered to alert the referring specialists early, at the onset of panhypopituitarism symptoms, including polyuria/polydipsia.

scholarly journals Risk factors for cancer-associated thrombosis in patients undergoing treatment with immune checkpoint inhibitors

2019 ◽  
Vol 38 (4) ◽  
pp. 1200-1206 ◽  
Author(s):  
Yosuke Ando ◽  
Takahiro Hayashi ◽  
Reiko Sugimoto ◽  
Seira Nishibe ◽  
Kaori Ito ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Heart Disease ◽  
Anticancer Agents ◽  
Immune Checkpoint ◽  
Odds Ratio ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
History Of ◽  
Cancer Associated Thrombosis

SummaryPurpose Anticancer agents are known to increase cancer-associated thrombosis (CAT) onset. CAT onset rate is reported to be 1.92% in cisplatin-based therapy, 6.1% in paclitaxel plus ramucirumab combination therapy, and 11.9% in bevacizumab monotherapy. Because immune checkpoint inhibitors (ICIs) cause a sudden increase in T cell number, an association between administration of these drugs and increase in CAT incidence is likely. However, the extent to which ICI administration affects CAT incidence remains unclear. Further, risk factors for CAT incidence have not yet been identified. The present study investigated CAT incidence and associated risk factors in patients receiving ICI. Methods Patients administered nivolumab or pembrolizumab at Fujita Health University Hospital from April 2017 to March 2018 were enrolled. We collected retrospective data regarding age, sex, cancer type, BMI, medical history, laboratory data at treatment initiation, medications, and computed tomography (CT) interpretations from electronic medical records. Results We identified 122 eligible participants from 135 patients receiving nivolumab or pembrolizumab. Ten patients (8.2%) developed CAT. A history of venous thromboembolism (VTE) or arterial thromboembolism (ATE) was a risk factor for CAT incidence (odds ratio: 6.36, P = 0.039). A history of heart disease may be a risk factor for CAT incidence (odds ratio 6.56, P = 0.052). Significantly higher usage of antiplatelet and anticoagulant therapy was noted in patients who developed CAT (60%) than in those who did not (13.4%, p < 0.01). Conclusion High (8.2%) CAT incidence during ICI administration suggested that ICI is not associated with a lower blood clot risk than other anticancer agents investigated in previous studies. For patients with VTE, ATE, or heart disease history, it is crucial to consider the possibility of CAT even with antiplatelet therapy.

scholarly journals Cardiotoxicity associated with immune checkpoint inhibitors: A retrospective analysis of patients at an academic tertiary care center

2020 ◽  
Author(s):  
Nida Waheed ◽  
Michael G. Fradley ◽  
David DeRemer ◽  
Ahmad Mahmoud ◽  
Chintan P. Shah ◽  
...  
Keyword(s):  
Heart Failure ◽  
Anticancer Agents ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Care Center ◽  
Tertiary Care ◽  
Data Repository ◽  
Tertiary Care Center ◽  
Pericardial Disease

Abstract Background Immune checkpoint inhibitors (ICIs) are a novel class of anticancer agents that have demonstrated clinical response for both solid and hematological malignancies. ICIs are associated with development of immune-related adverse events including cardiotoxicity. We estimated the incidence of ICI-related cardiotoxicity in patients treated with ICIs at a large, tertiary care center. Methods All patients with a cancer diagnosis who received any ICI treatment in the University of Florida’s Integrated Data Repository from 2011-2017 were included. Cardiotoxicity was defined as a new ICD diagnosis code for cardiomyopathy, heart failure, arrhythmia, heart block, pericardial disease, or myocarditis after initiation of ICI treatment. Results Of 102,701 patients with a diagnosis of malignancy, 424 patients received at least one ICI. Sixty-two (14.6%) patients were diagnosed with at least one possible form of cardiotoxicity after initiation of ICI therapy. Of the 374 patients receiving one ICI, 21 (5.6%) developed heart failure. Of the 49 patients who received two ICIs sequentially, three (6.1%) developed heart failure and/or cardiomyopathy. Cardiotoxicity was diagnosed at a median of 63 days after initial ICI exposure. One patient developed myocarditis 28 days after receiving nivolumab. Mortality in those who developed ICI-attributable cardiotoxicity was higher compared to those who did not (66.1% vs. 41.4%, odds ratio=2.77, 1.55-4.95, p=0.0006). Conclusions This study suggests that the incidence of ICI-related cardiotoxicity may be higher than previously reported.

scholarly journals Anti-PD-1, anti-VEGF, and temozolomide therapy in a patient with recurrent glioblastoma: a case report

2020 ◽  
Vol 48 (9) ◽  
pp. 030006052095139
Author(s):  
Can Chen ◽  
Wenwei Zuo ◽  
Pan Yang ◽  
Yanling Zhang
Keyword(s):  
Immune Checkpoint Inhibitors ◽  
Median Overall Survival ◽  
Checkpoint Inhibitors ◽  
Complete Response ◽  
Recurrent Glioblastoma ◽  
Vascular Endothelial ◽  
Case Presentation ◽  
Programmed Death ◽  
Endothelial Growth Factor

Background Patients suffering from postoperative recurrent glioblastoma have an extremely unfavorable outcome because there are no proven therapeutic options. The median overall survival for those with relapsed glioblastoma after surgery is only 7.5 months. Case presentation: Between March 2015 and October 2019, a 44-year-old female patient with recurrent glioblastoma was treated by our medical team. After several failed rounds of therapy, the patient was subsequently treated with the anti-programmed death (PD)-1 antibody nivolumab, anti-vascular endothelial growth factor (VEGF) antibody bevacizumab, and cytotoxic agent temozolomide. Results The patient showed a sustainable complete response to the regimen. To date, there have been no serious toxic side effects. As of October 2019 (the last follow-up), the patient has been in complete remission for 17 months since recurrence. Conclusion The experience of this complicated case indicates the possible application of immune checkpoint inhibitors, anti-angiogenesis agents, and cytotoxic reagents for recurrent glioblastoma. The administration of this three-agent regimen appears safe and effective. However, further clinical trials are warranted.

So slow, so fast, a case of nivolumab-induced hypothyroidism with subsequent rhabdomyolysis

Immunotherapy ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 625-628 ◽  
Author(s):  
Kamelah Abushalha ◽  
Sawsan Abulaimoun ◽  
Peter T Silberstein
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Death ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Thyroid Function Tests ◽  
Conventional Chemotherapy ◽  
Case Presentation ◽  
Normal Thyroid ◽  
Normal Thyroid Function ◽  
Programmed Cell Death 1

Background: Immunotherapy has revolutionized the treatment of cancer, but this has not come without a cost. Although immune checkpoint inhibitors are less toxic than conventional chemotherapy, they are associated with more frequent autoimmune side effects. Case presentation: We report a case of a patient with metastatic renal cell carcinoma who was treated with nivolumab and subsequently developed treatment related hypothyroidism with consequent rhabdomyolysis. Treatment with thyroxine resulted in resolution of the symptoms. Because of normal thyroid function tests before initiating nivolumab therapy and the absence of any other causes of hypothyroidism, it was safe to extrapolate a causal relationship between nivolumab and hypothyroidism. To date, this is the first reported case of a programmed cell death-1 inhibitor causing hypothyroidism, severe enough to induce rhabdomyolysis. Conclusion: Patients on nivolumab and other PD-1 inhibitors should be monitored and screened regularly for immune-related adverse events.

scholarly journals Cardiotoxicity associated with immune checkpoint inhibitors: A retrospective analysis of patients at an academic tertiary care center

2020 ◽  
Author(s):  
Nida Waheed ◽  
Michael G. Fradley ◽  
David DeRemer ◽  
Ahmad Mahmoud ◽  
Chintan P. Shah ◽  
...  
Keyword(s):  
Heart Failure ◽  
Anticancer Agents ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Beta Blockers ◽  
Care Center ◽  
Tertiary Care ◽  
Data Repository ◽  
Pericardial Disease

Abstract Background: Immune checkpoint inhibitors (ICIs) are a novel class of anticancer agents that have demonstrated clinical response for both solid and hematological malignancies. ICIs are associated with development of immune-related adverse events including cardiotoxicity. We estimated the incidence of ICI-related cardiotoxicity in patients treated with ICIs at a large, tertiary care center.Methods: All patients with a cancer diagnosis who received any ICI treatment in the University of Florida’s Integrated Data Repository from 2011-2017 were included. Cardiotoxicity was defined as a new ICD diagnosis code for cardiomyopathy, heart failure, arrhythmia, heart block, pericardial disease, or myocarditis after initiation of ICI treatment.Results: Of 102,701 patients with a diagnosis of malignancy, 424 patients received at least one ICI. Sixty-two (14.6%) patients were diagnosed with at least one possible form of cardiotoxicity after initiation of ICI therapy. Of the 374 patients receiving one ICI, 21 (5.6%) developed heart failure. Of the 49 patients who received two ICIs sequentially, three (6.1%) developed heart failure and/or cardiomyopathy. Cardiotoxicity was diagnosed at a median of 63 days after initial ICI exposure. One patient developed myocarditis 28 days after receiving nivolumab. Mortality in those who developed ICI-attributable cardiotoxicity was higher compared to those who did not (66.1% vs. 41.4%, odds ratio=2.77, 1.55-4.95, p=0.0006). There was no evidence that use of cardioprotective agents such as beta-blockers or statins was associated with lower rates of cardiotoxicity or mortality.Conclusions: This study suggests that the incidence of ICI-related cardiotoxicity may be higher than previously reported.

scholarly journals Durvalumab-induced myocarditis, myositis, and myasthenia gravis: a case report

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Jason Cham ◽  
Daniel Ng ◽  
Laura Nicholson
Keyword(s):  
Adverse Effects ◽  
Myasthenia Gravis ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Case Presentation ◽  
Progressive Dyspnea ◽  
Wide Range ◽  
New Onset

Abstract Background Immune checkpoint inhibitors are effective therapies for a wide range of malignancies. Their increased use has led to a wide range of immune-related adverse effects including skin, gastrointestinal, pulmonary, endocrine, cardiac, and neurologic complications. Case presentation We present the case of a 72-year-old Caucasian man with non-small cell lung cancer who was admitted for dyspnea after two cycles of durvalumab. He was found to have significantly elevated levels of serum creatinine kinase and troponin with a negative cardiac catheterization. During his hospitalization, he developed progressive dyspnea and new-onset axial weakness, ultimately leading to the diagnosis of durvalumab-induced myocarditis, myasthenia gravis, and myositis. Conclusion This is, to our knowledge, the first reported case of anti-programmed cell death ligand 1-induced combination of myocarditis, myasthenia gravis, and myositis. While the use of immunologic agents has resulted in overall improved cancer outcomes, their increased use has led to a vast spectrum of immune-related adverse effects. We review the diagnostic workup and management of patients with these immune-related adverse effects, underscoring the importance of early identification given the potential for rapid deterioration.

scholarly journals PD-L1, TMB, MSI, and Other Predictors of Response to Immune Checkpoint Inhibitors in Biliary Tract Cancer

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 558 ◽  
Author(s):  
Alessandro Rizzo ◽  
Angela Dalia Ricci ◽  
Giovanni Brandi
Keyword(s):  
Biliary Tract ◽  
Anticancer Agents ◽  
Biliary Tract Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Primary Liver Cancer ◽  
Tract Cancer ◽  
Predictors Of Response ◽  
Tumor Mutational Burden

Biliary tract cancer (BTC) represents the second most frequently diagnosed primary liver cancer worldwide following hepatocellular carcinoma, and the overall survival of patients with unresectable disease remains poor. In recent years, the advent of immune checkpoint inhibitors (ICIs) has revolutionized the therapeutic landscape of several malignancies with these agents, which have also been explored in advanced BTC, as monotherapy or in combination with other anticancer agents. However, clinical trials evaluating ICIs in BTC have shown conflicting results, and the clinical benefit provided by immunotherapy seems limited to a small subgroup of BTC patients. Thus, the identification of reliable predictors of the response to immunotherapy represents a significant challenge in this setting. This review provides an overview of the available evidence on the biomarkers predictive of the response to ICIs in patients with advanced BTC, especially focusing on programmed death-ligand 1 (PD-L1), tumor mutational burden (TMB), microsatellite instability (MSI), and other emerging biomarkers.

Encephalitis in a Patient With Melanoma Treated With Immune Checkpoint Inhibitors: Case Presentation and Review of the Literature

2020 ◽  
Vol 43 (7) ◽  
pp. 224-229 ◽  
Author(s):  
Aikaterini Gkoufa ◽  
Helen Gogas ◽  
Panagiotis T. Diamantopoulos ◽  
Dimitrios C. Ziogas ◽  
Mina Psichogiou
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Review Of The Literature ◽  
Case Presentation

scholarly journals A Comprehensive Review of US FDA-Approved Immune Checkpoint Inhibitors in Urothelial Carcinoma

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Fu-Shun Hsu ◽  
Chun-Hung Su ◽  
Kou-How Huang
Keyword(s):  
Urothelial Carcinoma ◽  
Anticancer Agents ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Locally Advanced ◽  
Background Information ◽  
Comprehensive Review ◽  
Platinum Based Chemotherapy ◽  
Us Fda

Few effective treatment options are available for patients with advanced or metastatic urothelial carcinoma (UC) after unsuccessful first-line platinum-based chemotherapy. To date, immune checkpoint inhibitors are novel therapeutic agents for UC treatment. From May 2016 to May 2017, five anti-PD-1/PD-L1 monoclonal antibodies received accelerated or regular approval from the US Food and Drug Administration (FDA) for the treatment of patients with locally advanced or metastatic UC. The present comprehensive review presents the background information of these five US FDA-approved anticancer agents to provide a basic but concise understanding of these agents for advanced studies. We summarize their immune checkpoint mechanisms, clinical efficacy, recommended usage protocols, adverse events, and the limitations of the PD-L1 biomarker assays.

scholarly journals Risk of immunotherapy-related narcolepsy in genetically predisposed patients: a case report of narcolepsy after administration of pembrolizumab

2020 ◽  
Vol 8 (2) ◽  
pp. e001164
Author(s):  
Yutaka Natori ◽  
Eisaku Sasaki ◽  
Shu Soeda ◽  
Shigenori Furukawa ◽  
Yusuke Azami ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Human Leucocyte Antigen ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Case Presentation ◽  
Stage Ivb ◽  
Hypocretin 1

BackgroundImmune-related adverse events associated with immune checkpoint therapy cause autoimmune disease-like symptoms. People who carry specific genotypes or haplotypes of human leucocyte antigen (HLA) are known to be predisposed to develop autoimmune diseases including narcolepsy. Immunotherapy could be a trigger to develop narcolepsy in predisposing HLA positive patients.Case presentationA 66-year-old woman with stage IVB endometrial carcinosarcoma experienced daytime sleepiness and temporary muscle weakness 14 days after the administration of an immune checkpoint inhibitor, pembrolizumab. These were consistent with the main symptoms of narcolepsy with cataplexy. This patient carried a highly predisposing HLA haplotype for narcolepsy; HLA-DQB1*06:02, DRB1*15:01, DQA1*01:02 and DRB5*01:01:01. A hypocretin-1/orexin-A concentration in the patient’s cerebrospinal fluid was low at 9.6 pg/mL in ELISA, and 155.5 pg/mL in radioimmunoassay that was below the normal level of 200 pg/mL. Therefore, she was diagnosed with narcolepsy tentatively according to the International Classification of Sleep Disorders, third edition diagnostic criteria for narcolepsy. The onset of narcolepsy in the 60s is very rare, and narcoleptic symptoms in our patient were likely to be caused by pembrolizumab.ConclusionsThis case suggests that treatment with immune checkpoint inhibitors potentially causes narcolepsy in genetically predisposed patients.

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